This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary SIVsm isolates are significantly less pathogenic in Rh than the serially passaged SIVmac251/239. Our hypothesis is that the use of SIVsm strains representing different clades will generate a better model for AIDS pathogenesis. Our objective is to construct and characterize in vitro and in vivo infectious molecular clones of SIVsm strains belonging to different, well-defined phylogenetic lineages (clades). Total RNA from the sera of SIV infected animals M926, M946 (lineage 2), D215 (Lineage 6), FTQ (Lineage 5) and M923 (Lineage 1, recombinant strain) was isolated. Full length sequencing of these viruses is completed Other 10 new SIVsmm full length genomes has been generated. An infectious clone of SIVsmmM926 was obtained and is currently tested in vitro and in vivo. Remaining clone construction is in progress. An array of infectious molecular clones, which are better controlled by the immune system will provide enhanced and very much needed tools to the research community for AIDS immunopathogenesis and vaccine development investigating heterotypic protection in Rh.